Transcriptomics

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Id proteins synchronize stemness and anchorage to the niche of neural stem cells


ABSTRACT: Stem cell functions require activation of stem cell-intrinsic transcriptional programs as well as intimate extracellular interactions with a niche microenvironment. How the core pluripotency transcriptional machinery controls residency of stem cells in the niche microenvironment is unknown. Here we show that the helix loop helix transcriptional regulators Id (Inhibitors of DNA binding) are the master regulators that coordinate stem cell activities with anchorage of neural stem cells (NSCs) to the embryonic and postnatal niche. Conditional inactivation of Id genes (Id1, Id2 and Id3) in the mouse NSC compartment triggered detachment of embryonic and post-natal NSCs from the ventricular and vascular niche respectively, followed by premature differentiation. Through an unbiased interrogation of the gene modules directly targeted by deletion of Id genes in NSCs, we discovered that Id proteins repress the bHLH-mediated activation of Rap1GAP, thus serving to maintain the GTPase activity of RAP1, a key mediator of cell adhesion. Preventing the elevation of Rap1GAP efficiently countered the consequences of Id loss on NSC-niche interaction and stem cell identity. Thus, by preserving anchorage to the extracellular environment of NSCs, Id activity synchronizes NSC functions to residency in the specialized niche.

ORGANISM(S): Mus musculus

PROVIDER: GSE36488 | GEO | 2012/03/15

SECONDARY ACCESSION(S): PRJNA153527

REPOSITORIES: GEO

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